Nature Medicine
- 12, 1213 - 1219 (2006)
Published online: 1 October 2006; | doi:10.1038/nm1404
In vivo imaging of lymph node metastasis with telomerase-specific replication-selective adenovirusHiroyuki Kishimoto1, 2, Toru Kojima1, 2, Yuichi Watanabe1, 3, Shunsuke Kagawa1, 2, Toshiya Fujiwara1, 2, Futoshi Uno1, 2, Fuminori Teraishi1, 2, Satoru Kyo4, Hiroyuki Mizuguchi5, Yuuri Hashimoto3, Yasuo Urata3, Noriaki Tanaka1 & Toshiyoshi Fujiwara1, 21
Division of Surgical Oncology, Department of Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Okayama 700-8558, Japan. 2
Center for Gene and Cell Therapy, Okayama University Hospital, 2-5-1 Shikata-cho, Okayama 700-8558, Japan. 3
Oncolys BioPharma, Inc., 3-16-33 Roppongi, Minato-ku, Tokyo 106-0032, Japan. 4
Department of Obstetrics and Gynecology, Kanazawa University School of Medicine, 13-1 Takara-machi, Kanazawa 920-8641, Japan. 5
Laboratory of Gene Transfer and Regulation, National Institute of Biomedical Innovation, 7-6-8 Saito-Asagi, Ibaraki, Osaka 567-0085, Japan.
Correspondence should be addressed to Toshiyoshi Fujiwara toshi_f@md.okayama-u.ac.jp Currently available methods for detection of tumors in vivo such as computed tomography and magnetic resonance imaging are not specific for tumors. Here we describe a new approach for visualizing tumors whose fluorescence can be detected using telomerase-specific replication-competent adenovirus expressing green fluorescent protein (GFP) (OBP-401). OBP-401 contains the replication cassette, in which the human telomerase reverse transcriptase (hTERT) promoter drives expression of E1 genes, and the GFP gene for monitoring viral replication. When OBP-401 was intratumorally injected into HT29 tumors orthotopically implanted into the rectum in BALB/c nu/nu mice, para-aortic lymph node metastasis could be visualized at laparotomy under a three-chip color cooled charged-coupled device camera. Our results indicate that OBP-401 causes viral spread into the regional lymphatic area and selectively replicates in neoplastic lesions, resulting in GFP expression in metastatic lymph nodes. This technology is adaptable to detect lymph node metastasis in vivo as a preclinical model of surgical navigation.
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